Evaluation of Osteoporotisis Drugs by Histological, Biochemical Approach in Experimental Osteoporosis Model

实验性骨质疏松模型中通过组织学、生化方法评价骨质疏松药物

• 批准号: 16591470
• 负责人: ITOI Eiji
• 金额: $ 0.9万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591470/
• 关键词: vitamin D; osteoporosis; muscle strength; muscle fatigue; ビタミンK

Several recent studies have demonstrated that vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall-prevention are still unclear. In this study, we investigated the effects of alfacalcidol (1α(OH)D3) on muscle strength, muscle fatigue, and bone mineral density (BMD) in normal and ovariectomized rats.Following ovariectomy (OVX) or sham operation in 7-month-old female Wistar rats, alfacalcidol (0.1 μg/kg/day) or its vehicle was administered orally for 4 weeks. On the day after the final administration, the distal end of the Achilles' tendon was cut and attached to a force transducer under general anesthesia, and the sciatic nerve was exposed and electrically stimulated for 20 cycles. The maximum contraction tension of the calf muscles for each stimulation cycle was measured to evaluate muscle strength. Muscle fatigue at each stimulation cycle was evaluated as the percentage strength at each cycle to the initial contraction strength. Muscle strength and fatigue were then normalized using the body weight. After the measurement of muscle strength and fatigue, the right femur was harvested to measure the BMD at the distal third of the femur by dual energy x-ray absorptiometry.Alfacalcidol administration significantly increased the maximum muscle strength in the sham-operated and the OVX groups compared to their respective control groups. However, alfacalcidol administration did not significantly affect muscle fatigue in these groups. The BMD in the alfacalcidol-treated OVX group was significantly higher than that in the vehicle-treated OVX group.We conclude that alfacalcidol increases muscle strength, but does not affect muscle fatigue in the rat model. The effectiveness of vitamin D in preventing fractures may be partly due to its effect on muscle strength in addition to its known effect on bone metabolism.

最近的一些研究表明，维生素D不仅会影响骨骼，还会影响肌肉以防止跌落和骨质疏松性骨折。但是，这些对肌肉的影响和秋天预防的机制尚不清楚。在这项研究中，我们研究了恶藻醇（1α（OH）D3）对正常和卵巢切除大鼠的肌肉强度，肌肉疲劳和骨矿物质密度（BMD）的影响。遵循7个月大的女性Wistar rats，Alfacalcidol（0.1 kg）的卵巢切除术（OVX）或假手术（OVX）或假手术。 4周。在最终给药后的第二天，在全身麻醉下切割跟腱的远端并附着在力传感器上，并暴露了坐骨神经和20个循环的电刺激。测量每个刺激周期的小腿肌肉的最大收缩张力以评估肌肉强度。在每个模拟周期中，将肌肉疲劳评估为每个周期到初始合同强度的百分比。然后使用体重将肌肉力量和疲劳归一化。在测量肌肉强度和疲劳之后，通过双能量X射线绝对ePiementry.alfacalcidol施用回收了右股骨，以测量股骨不同的三分之一的BMD。与其各自的对照组相比，Alfacalcilolcidol的给药可显着提高假手术和OVX组的最大肌肉强度。但是，冒恶甲醇的给药并未显着影响这些组的肌肉疲劳。恶肽醇处理的OVX组中的BMD明显高于载体处理的OVX组。我们包括恶藻酚会增加肌肉强度，但不会影响大鼠模型中的肌肉疲劳。维生素D在预防裂缝中的有效性可能部分是由于其对肌肉强度的影响，除了其对骨代谢的已知作用。